The Genome-wide Methylation Profile of CD4+ T Cells From Individuals With Human Immunodeficiency Virus (HIV) Identifies Distinct Patterns Associated With Disease Progression.
Clin Infect Dis
; 72(9): e256-e264, 2021 05 04.
Article
en En
| MEDLINE
| ID: mdl-32712664
ABSTRACT
BACKGROUND:
Human genetic variation-mostly in the human leukocyte antigen (HLA) and C-C chemokine receptor type 5 (CCR5) regions-explains 25% of the variability in progression of human immunodeficiency virus (HIV) infection. However, it is also known that viral infections can modify cellular DNA methylation patterns. Therefore, changes in the methylation of cytosine-guanine (CpG) islands might modulate progression of HIV infection.METHODS:
In total, 85 samples were analyzed 21 elite controllers (EC), 21 subjects with HIV before combination antiretroviral therapy (cART) (viremic, 93 325 human immunodeficiency virus type 1 [HIV-1] RNA copies/mL) and under suppressive cART (cART, median of 17 months, <50 HIV-1 RNA copies/mL), and 22 HIV-negative donors (HIVneg). We analyzed the methylation pattern of 485 577 CpG in DNA from peripheral CD4+ T lymphocytes. We selected the most differentially methylated gene (TNF) and analyzed its specific methylation, messenger RNA (mRNA) expression, and plasma protein levels in 5 individuals before and after initiation of cART.RESULTS:
We observed 129 methylated CpG sites (associated with 43 gene promoters) for which statistically significant differences were recorded in viremic versus HIVneg, 162 CpG sites (55 gene promoters) in viremic versus cART, 441 CpG sites (163 gene promoters) in viremic versus EC, but none in EC versus HIVneg. The TNF promoter region was hypermethylated in viremic versus HIVneg, cART, and EC. Moreover, we observed greater plasma levels of TNF in viremic individuals than in EC, cART, and HIVneg.CONCLUSIONS:
Our study shows that genome methylation patterns vary depending on HIV infection status and progression profile and that these variations might have an impact on controlling HIV infection in the absence of cART.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Infecciones por VIH
/
VIH-1
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Clin Infect Dis
Asunto de la revista:
DOENCAS TRANSMISSIVEIS
Año:
2021
Tipo del documento:
Article
País de afiliación:
España